3-hydroxypropyl methanesulfonate -Drug Synthesis Database

【结构式】

【分子编号】50262

【品名】3-hydroxypropyl methanesulfonate

【CA登记号】

【分子式】C₄H₁₀O₄S

【分子量】154.187

【元素组成】C 31.16% H 6.54% O 41.51% S 20.8%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XXI)

The desulfurization of (XXI) with H2O2 and CaCO3 gives the chiral allylpiperidine (XXII), which is epoxidized by oxidation with OsO4, reaction of Ts-OH and treatment with K2CO3 to yield the epoxide (XXIII). The condensation of (XXIII) with quinazolinone (XXIV) by means of KOH in methanol affords the substituted propanol (XXV), which is oxidized with DMP to provide the propanone derivative (XXVI). Finally, compound (XXVI) is deprotected by treatment with refluxing 6N HCl to give the target febrifugine.

参考文献中间体

合成目标

【1】 Taniguchi, T.; Ofasawara, K.; A diastereocontrolled synthesis of (+)-febrifugine: A potent antimalarial piperidine alkaloid. Org Lett 2000, 2, 20, 3193.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXI)	50262	3-hydroxypropyl methanesulfonate	C₄H₁₀O₄S	详情	详情
(XXII)	51264	benzyl (2R,3S)-2-allyl-3-(benzyloxy)-1-piperidinecarboxylate	C₂₃H₂₇NO₃	详情	详情
(XXIII)	51265	benzyl (2R,3S)-3-(benzyloxy)-2-(2-oxiranylmethyl)-1-piperidinecarboxylate	C₂₃H₂₇NO₄	详情	详情
(XXIV)	14634	4(3H)-quinazolinone	C₈H₆N₂O	详情	详情
(XXV)	51266	benzyl (2R,3S)-3-(benzyloxy)-2-[2-hydroxy-3-[4-oxo-3(4H)-quinazolinyl]propyl]-1-piperidinecarboxylate	C₃₁H₃₃N₃O₅	详情	详情
(XXVI)	51267	benzyl (2R,3S)-3-(benzyloxy)-2-[2-oxo-3-[4-oxo-3(4H)-quinazolinyl]propyl]-1-piperidinecarboxylate	C₃₁H₃₁N₃O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Conjugate addition of 4-tolylmagnesium bromide (II) to anhydroecgonine methyl ester (I) afforded regioselectively the 2-beta-carbomethoxy-3-beta-aryl tropane (III). Hydrolysis of the ester function of (III) in aqueous dioxan gave the corresponding acid (IV). Treatment of (IV) with POCl3 yielded the acid chloride (V), which was condensed with 1,3-propanediol monomesylate (VI), yielding ester (VII). Finally, nucleophilic displacement of the mesylate group of (VII) with tetrabutylammonium fluoride in refluxing THF afforded the title fluoropropyl ester.

参考文献中间体

合成目标

【1】 Gu, X.-H.; et al.; Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: Potential positron emission tomography (PET) imaging agents for the dopamine transporter. Bioorg Med Chem Lett 2001, 11, 23, 3049.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	21118	methyl (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate		C₁₀H₁₅NO₂	详情	详情
(II)	35657	bromo(4-methylphenyl)magnesium	4294-57-9	C₇H₇BrMg	详情	详情
(III)	50267	methyl (1R,2S,3S,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate		C₁₇H₂₃NO₂	详情	详情
(IV)	50268	(1R,2S,3S,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylic acid		C₁₆H₂₁NO₂	详情	详情
(V)	50269	(1R,2S,3S,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carbonyl chloride		C₁₆H₂₀ClNO	详情	详情
(VI)	50262	3-hydroxypropyl methanesulfonate		C₄H₁₀O₄S	详情	详情
(VII)	50270	3-[(methylsulfonyl)oxy]propyl (1R,2S,3S,5S)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate		C₂₀H₂₉NO₅S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VII)

Conjugate addition of 4-(trimethylsilyl)phenylmagnesium bromide (II) to anhydroecgonine methyl ester (I) afforded regioselectively the 2-beta-carbomethoxy-3-beta-aryl tropane (III). Iododesilylation of (III) using ICl or iodine in the presence of AgBF4 gave the iodophenyl derivative (IV). Hydrolysis of the ester function of (IV) in aqueous dioxan yielded the corresponding acid (V). Treatment of (V) with POCl3 provided the acid chloride (VI), which was condensed with 1,3-propanediol monomesylate (VII) to yield ester (VIII). Finally, nucleophilic displacement of the mesylate group of (VIII) with tetrabutylammonium fluoride in refluxing THF afforded the title fluoropropyl ester.

参考文献中间体

合成目标

【1】 Gu, X.-H.; et al.; Synthesis and biological evaluation of a series of novel N- or O-fluoroalkyl derivatives of tropane: Potential positron emission tomography (PET) imaging agents for the dopamine transporter. Bioorg Med Chem Lett 2001, 11, 23, 3049.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	21118	methyl (1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate	C₁₀H₁₅NO₂	详情	详情
(II)	50257	bromo[4-(trimethylsilyl)phenyl]magnesium	C₉H₁₃BrMgSi	详情	详情
(III)	50258	methyl (1R,2S,3S,5S)-8-methyl-3-[4-(trimethylsilyl)phenyl]-8-azabicyclo[3.2.1]octane-2-carboxylate	C₁₉H₂₉NO₂Si	详情	详情
(IV)	50259	methyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	C₁₆H₂₀INO₂	详情	详情
(V)	50260	(1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid	C₁₅H₁₈INO₂	详情	详情
(VI)	50261	(1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carbonyl chloride	C₁₅H₁₇ClINO	详情	详情
(VII)	50262	3-hydroxypropyl methanesulfonate	C₄H₁₀O₄S	详情	详情
(VIII)	50263	3-[(methylsulfonyl)oxy]propyl (1R,2S,3S,5S)-3-(4-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate	C₁₉H₂₆INO₅S	详情	详情

Extended Information